The objective of the proposed study (a follow-up of the findings of an earlier Grant, # 2 RO 1 MH 20500-02) is to pursue the indication that norepinephrine in the limbic system (notably n. accumbens, hypothalamus, spectum, hippocampus and olfactory regions) is central to the mechanism of action of the chronically administered neuroleptic (anti-psychotic) drugs (e.g. haloperidol, chlorpromazine and clozapine). Steady-state levels as well as turnover estimations of norepinephrine and dopamine will be performed. In addition to norepinephrine and dopamine, homovanillic acid, MHPG, acetylcholine, choline acetyltransferase, 5-hydroxytryptamine and 5-HIAA will also be studied. A comparison of chronic vs acute treatment with the two clinically different classes of neuroleptics (classical vs "silent") is planned. The methods used are mainly micro-analytical in nature, and are most suitable for estimations of large numbers of small samples. Dopamine, norepinephrine and acetylcholine are analyzed radio-enzymatically; serotonin, 5-HIAA, MHPG and homovanillic acid are determined fluorometrically; choline acetyltransferase is assayed utilizing radioactive acetyl-coenzyme A. The brain dissection procedures utilized (for cat, rabbit, rat and human) are of a highly refined nature and yield distinct regions suitable for biochemical characterization. The proposed research is expected to provide new and applicable information not only to the anatomical site(s) of action of neuroleptics but also should contribute to our knowledge of the mechanisms involved in their antipsychotic and extra-pyramidal actions.